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Temsirolimus Adventitial Delivery to Improve Angiographic Outcomes Below the Knee (TANGO) (TANGO)

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ClinicalTrials.gov Identifier: NCT02908035
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Mercator MedSystems, Inc.

Brief Summary:
This is a prospective, multi-center, randomized, dose escalation study to document the effects of adventitial delivery of temsirolimus (Torisel) after revascularization of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).

Condition or disease Intervention/treatment Phase
Chronic Limb Ischemia Drug: Temsirolimus Drug: Saline Phase 2

Detailed Description:
This is a prospective, multi-center, randomized, dose escalation study to document the effects of adventitial delivery of temsirolimus (Torisel) after revascularization of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 60 patients (20 low-dose, 20 high-dose and 20 control) at up to 15 sites in the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of temsirolimus in reducing intimal hyperplasia, inflammatory markers and composite safety endpoints in patients with clinical evidence of chronic critical limb ischemia after revascularization of one or more angiographically significant lesion(s) in below-knee popliteal or tibial vessels.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: TANGO: Temsirolimus Dventitial Delivery to Improve ANGiographic Outcomes Below the Knee
Actual Study Start Date : March 3, 2017
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active Comparator: Temsirolimus Delivery High Dose
High-Dose Group: 0.4 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
Drug: Temsirolimus
After completion of revascularization therapy and any decision to place stents, patients will be qualified for final enrollment in the study and will be treated with the investigational drug or saline. Investigators will be blinded to assignment.
Other Name: Torisel

Active Comparator: Active Comparator: Temsirolimus Delivery Low Dose
Low-Dose Group: 0.1 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
Drug: Temsirolimus
After completion of revascularization therapy and any decision to place stents, patients will be qualified for final enrollment in the study and will be treated with the investigational drug or saline. Investigators will be blinded to assignment.
Other Name: Torisel

Placebo Comparator: Placebo Comparator: Saline Delivery
Control Group: Saline/contrast (80% normal saline for injection:20% non-ionic contrast) The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
Drug: Saline
After completion of revascularization therapy and any decision to place stents, patients will be qualified for final enrollment in the study and will be treated with the investigational drug or saline. Investigators will be blinded to assignment.




Primary Outcome Measures :
  1. Freedom from MALE-POD [ Time Frame: Up to 30 days post-procedure ]
    Freedome from MALE-POD at 30 days.

  2. Transverse-view vessel area loss percentage (TVAL%) of the target lesion [ Time Frame: Within 6 months post-procedure ]
    Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any TLR of the target lesion before 6 months.


Secondary Outcome Measures :
  1. Freedom from a composite of all-cause death, MALE and unplanned minor amputation in target limb [ Time Frame: Up to 30 days post-procedure ]
    Freedom from a composite of all-cause death within 30 days from the index procedure, major adverse limb event (MALE) of the target limb, unplanned minor amputation in the target limb, and clinically driven target lesion revascularization (CD-TLR) within 6 months.

  2. Freedom from a composite of death, unplanned minor amputation, clinically driven TLR, and major adverse limb events (MALE) [ Time Frame: Up to 12 months post-procedure ]
    Freedom from a composite of death, unplanned minor amputation, clinically driven TLR, and major adverse limb events (MALE) up to 12 months from the procedure for all subjects.

  3. Freedom from Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months post-procedure ]
    Freedom from serious adverse events (SAE) to 12 months from the procedure for all subjects.

  4. Event-free survival [ Time Frame: Up to 12 months post-procedure ]
    Event-free survival to 12 months from the procedure for all subjects.

  5. Improvement in % diameter stenosis and maximum late lumen loss (LLL) of the target lesion [ Time Frame: Up to 6 months post-procedure ]
    6-month improvement % diameter stenosis (%DS) of the target lesion (TL) and the maximum late lumen loss for the lesion (LLL) will be assessed by Quantitative Vascular Angiography.

  6. Improvement in luminal volume by intravascular ultrasound (IVUS) [ Time Frame: Up to 6 months post-procedure ]
    6-month improvement in luminal volume as measured by intravascular ultrasound (IVUS) within the TL (subgroup analysis).

  7. Composite of major amputation, target vessel occlusion or CD-TLR [ Time Frame: Up to 12 months post-procedure ]
    A composite at 12 months of freedom from major amputation, target vessel occlusion, or CD-TLR.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Screening Criteria:

  • Age ≥18 years and <90 years
  • Patient has been informed of the nature of the study, agrees to participate and has signed an IRB approved consent form
  • Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a highly effective method of birth control (See Section 12.2) one month preceding and 12 months following study treatment
  • Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the distal segment (P3) of the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 3, 4 or 5
  • Life expectancy >1 year in the Investigator's opinion

Angiographic Criteria:

  • Target vessel(s) diameter ≥2 mm and ≤8 mm
  • Single or multiple atherosclerotic lesion(s) ≥70% in at least one below-knee popliteal or tibial target vessel including the tibioperoneal trunk that totals up to no greater than 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)
  • Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound, if a wound is present at baseline

Exclusion Criteria:

• Screening Criteria

  • Patient is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint
  • Patient unwilling or unlikely to comply with visit schedule
  • Patients who are incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial
  • Patient is already receiving or planned to receive systemic immunotherapy, chemotherapy, or steroids (however, inhaled steroids for asthma treatment or topical steroid uses are allowed)
  • Patient has a bilirubin level of >1.5xULN
  • Recent (<30 days prior to study procedure) myocardial infarction
  • Cerebrovascular accident <60 days prior to the study procedure
  • Planned major (above the ankle) target limb amputation
  • Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers (<25mm) are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
  • Inability to receive temsirolimus or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions Estimated glomerular filtration rate (eGFR, calculated from serum creatinine using an isotope dilution mass spectrometry (IDMS)-traceable equation) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
  • Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature or non-ischemic in origin

Angiographic/Procedural Criteria

  • Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries (P1 and P2) in which there is failure to successfully treat and obtain a <30% residual stenosis post-revascularization, with bailout stenting as needed (in-flow lesions should be treated prior to treating the target lesion)
  • Target lesion length is >30 cm as measured from proximal normal vessel to distal normal vessel
  • Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-target lesions) >30 cm
  • Use of alternative therapy, e.g. radiation therapy, drug-eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) as part of the target lesion treatment or during the previous 2 months within the target lesion
  • Previously implanted stent in the TL(s)
  • Aneurysm in the target vessel
  • Acute thrombus in the target limb
  • Failure to cross the TL with a guide wire; however, subintimal wire crossing is allowed
  • Heavy eccentric or concentric calcification at target lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02908035


Contacts
Contact: Kristen L Poole, PhD 510-564-7761 ext 818 kpoole@mercatormed.com

Locations
United States, Arkansas
Arkansas Heart Hospital Recruiting
Little Rock, Arkansas, United States, 72211
Contact: Stacey Tefteller    501-978-8621    Stacey.Tefteller@arheart.com   
Principal Investigator: Ian Cawich, MD         
United States, California
St. Joseph Hospital of Orange Heart and Vascular Center Not yet recruiting
Orange, California, United States, 92868
Contact: Sandy Chung       sandy.chung@stjoe.org   
Principal Investigator: Mahmood K. Razavi, MD         
United States, Colorado
Denver Veterans Administration Hospital Recruiting
Denver, Colorado, United States, 80220
Contact: Caitlin Kielhorn    303-399-8020 ext 4019    caitlin.kielhorn@ucdenver.edu   
Principal Investigator: Ehrin J Armstrong, MD MSc FACC FSCAI FSVM         
United States, Illinois
Advocate Christ Medical Center Recruiting
Oak Lawn, Illinois, United States, 60453
Contact: Christopher Doherty, RN BSN CCRN    708-684-4618    christopher.doherty@advocatehealth.com   
Principal Investigator: Jaafer Golzar, MD         
United States, Ohio
University Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: Maria Uchbar       Maria.Zeuli@uhhospitals.org   
Principal Investigator: Medhi Shishehbor, DO, PHD, MPH         
United States, Pennsylvania
Einstein Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19141
Contact: Kinnari Murthy, MPH    215-456-6736    MurthyK@einstein.edu   
Principal Investigator: Jon George, MD         
United States, South Dakota
Sanford Research Recruiting
Sioux Falls, South Dakota, United States, 57101
Contact: Karla Reilly, RN    605-312-7329    karla.reilly@sanfordhealth.org   
Principal Investigator: Angelo Santos, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Ivan Marin    520-445-9352    Ivan.Marin@bcm.edu   
Principal Investigator: Miguel Montero-Baker, MD         
Sponsors and Collaborators
Mercator MedSystems, Inc.

Responsible Party: Mercator MedSystems, Inc.
ClinicalTrials.gov Identifier: NCT02908035     History of Changes
Other Study ID Numbers: CIP0214
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Ischemia
Pathologic Processes
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents